恩替卡韦联合血浆置换治疗慢性乙型重型肝炎的研究

目的初步探讨恩替卡韦联合血浆置换治疗慢性乙型重型肝炎患者的疗效。方法选取40例慢性乙型重型肝炎患者,在常规内科治疗及恩替卡韦0.5 mg/d抗病毒治疗基础上联合血浆置换治疗。同时选取38例慢重肝患者为对照组,给予常规内科治疗及恩替卡韦0.5 mg/d抗病毒治疗。比较2组患者在慢性乙型重型肝炎早、中和晚期存活率的差异。结果联合血浆置换组生存率为72.5%,而对照组生存率为50%(χ2=4.168,P=0.041)。其中,中期慢重肝患者联合血浆置换治疗,其生存率为72.2%,而对照组生存率为38.9%(χ2=4.050,P=0.044),早期和晚期慢重肝患者联合血浆置换治疗,其生存率与对照组比差异无统计学意义(P0.05)。结论慢性乙型重型肝炎中期患者采用恩替卡韦联合血浆置换治疗能提高患者生存率。     

恩替卡韦对慢性乙型病毒性肝炎患者TNF-α及CEA水平的影响

目的:探究恩替卡韦对慢性乙型病毒性肝炎患者TNT-α,CEA水平及临床疗效的影响研究。方法:选取我院慢性乙型病毒性肝炎患者39例,随机分为实验组(20例)和对照组(19例)。对照组予拉米夫定治疗,实验组予恩替卡韦治疗。观察并比较两组患者治疗前后血清TNF-α,CEA及肝功能水平变化以及HBV DNA转阴率。结果:实验组患者的总有效率(95.0%)高于对照组(73.7%),差异有统计学意义(P0.05);与治疗前相比,两组患者治疗后血清ALT,AST及TNF-α水平均下降,差异具有统计学意义(P0.05);与对照组比较,实验组患者治疗后血清ALT,AST及TNF-α水平均下降,差异具有统计学意义(P0.05);与对照组比较,实验组患者HBV DNA转阴率较高,差异有统计学意义(P0.05)。结论:恩替卡韦治疗慢性乙肝病毒性肝炎的临床效果较好,能够降低TNT-α水平,提高HBV DNA转阴率,改善患者肝功能,值得临床推广应用。     

恩替卡韦治疗HBeAg 阳性乙型肝炎临床观察

目的:探讨恩替卡韦治疗HBeAg阳性乙型肝炎的疗效与安全性。方法:140例慢性乙肝患者随机分为2组:观察组予恩替卡韦0.5 mg/d,对照组予拉米夫定100 mg/d,疗程均为48周。观察两组HBV DNA阴转率、ALT复常率、HbeAg血清转换率以及不良反应发生情况。结果:在治疗12周后,观察组与对照组HBV DNA阴转率分别为47.1%、22.9%(P<0.01),ALT复常率分别为51.4%、31.4%(P<0.05),在治疗48周后,观察组与对照组HBV DNA阴转率分别为88.6%、48.6%(P<0.01),ALT复常率分别为90.0%、72.9%(P<0.01)。HbeAg血清转换率无统计学差异,两组患者未见严重不良反应。结论:恩替卡韦治疗HBeAg阳性乙肝患者,较拉米夫定起效快、作用强,且安全性好。     

拉米夫定联合胸腺肽α1治疗慢性重型乙型肝炎临床观察

目的:观察拉米夫定联合胸腺肽α1治疗慢性重型乙型肝炎的疗效.方法:22例慢性重型乙型肝炎患者在综合性护肝治疗基础上,加服拉米夫定100mg,每天1次;同时皮下注射胸腺肽α1针1.6 mg,每周3次,疗程4～12周.结果:治疗前后患者肝功能明显改善,血清总胆红素水平从(326±189)μmol/L降至(36±16.2)μmol/L,丙氨酸转氨酶水平从(367±289)U/L降至(21±7.5)U/L,凝血酶原时间从(31±11.5)秒缩短至(15±3)秒.有16例患者治疗前检测到HBV DNA,其中10例治疗后阴转(低于1×102copies/ml),其余6例无明显变化(持续105～106 copies/ml).22例患者存活18例,总有效率81.8%.结论:拉米夫定联合胸腺肽α1治疗慢性重型乙型肝炎有效.     

谷氨酰胺联合恩替卡韦对病毒型肝硬化小鼠肝脏病变指标及免疫水平的影响

目的:探讨谷氨酰胺联合恩替卡韦对病毒型肝硬化小鼠肝脏病变指标及免疫水平的影响。方法:将60只健康雄性BABL/cJ小鼠按照随机数字表法分为模型组、谷氨酰胺组,谷氨酰胺联合恩替卡韦组(联合组),对照组,每组15只。采用高压水注射方法将50μL HBV质粒通过尾静脉注入模型组、谷氨酰胺组,联合组三组小鼠体内,然后腹腔注射50%CCI4(5 m L/kg)以构建肝硬化模型小鼠。对照组经尾静脉注射50μL生理盐水,然后腹腔注射生理盐水(5 m L/kg)。谷氨酰胺组接受谷氨酰胺(0.5 m L/10g)治疗,联合组接受恩替卡韦联合谷氨酰胺(0.5 m L/10 g)治疗,对照组、模型组接受生理盐水(0.5 m L/10g)治疗,每天1次,治疗周期均为4周。比较四组小鼠的肝功能、病毒载量、肝纤维化指标、免疫功能。结果:成模后,模型组、谷氨酰胺组、联合组的病毒载量、ALT、AST、HA、PIIIP水平无统计学差异(P0.05);治疗4周后,谷氨酰胺组、联合组两组病毒载量、ALT、AST、HA、PIIIP水平显著下降,且联合组病毒载量、ALT、AST、HA、PIIIP水平低于谷氨酰胺组,差异具有统计学差异(P0.05);治疗4周后,谷氨酰胺组病毒载量、ALT、AST、HA、PIIIP水平低于模型组,差异具有统计学差异(P0.05);治疗4周后,谷氨酰胺组、联合组两组脾脏指数、CD4+、CD4+/CD8+百分率升高组脾脏指数、CD4+、CD4+/CD8+百分率高于谷氨酰胺组,差异具有统计学差异(P0.05)。结论:谷氨酰胺联合恩替卡韦可改善病毒型肝硬化小鼠肝脏肝功能,减轻组织纤维化,并有助于增强其免疫功能。     

益气软肝方联合恩替卡韦治疗慢性肝炎肝纤维化的临床研究

目的:探讨益气软肝方联合恩替卡韦治疗慢性肝炎肝纤维化的临床效果。方法:选择2012年9月至2015年2月在我院内科治疗的慢性肝炎肝纤维化患者98例,采用随机抽签方法分为治疗组与对照组各49例,对照组给予恩替卡韦治疗,治疗组给予益气软肝方联合恩替卡韦治疗,都治疗3个月。对治疗后两组疗效、肝功能指标及肝纤维化指标进行检测与比较。结果:治疗后治疗组的总有效率为98.0%,对照组为85.7%,治疗组总有效率明显高于对照组(P0.05)。与治疗前相比,治疗后两组肝功能指标均有所改善(P0.05),治疗后两组肝功能指标对比差异不明显(P0.05)。两组治疗后的血清HA、CⅣ、PCⅢ和LN值都明显低于治疗前(P0.05),同时与对照组相比,治疗后治疗组的血清HA、CⅣ、PCⅢ和LN值明显较低(P0.05)。结论:益气软肝方联合恩替卡韦治疗慢性肝炎肝纤维化能提高治疗疗效,改善肝功能指标及肝纤维化指标,其作用机制可能与降低肝纤维化因子的释放有关。     

恩替卡韦联合自拟血府逐瘀汤治疗慢性乙型肝炎肝纤维化患者的疗效分析

目的:探讨慢性乙型肝炎肝纤维化采用恩替卡韦联合自拟血府逐瘀汤治疗的临床疗效。方法:将86例慢性乙型肝炎肝纤维化患者按照随机数字表随机分为分为观察组(n=43例)和对照组(n=43例),对照组给予口服恩替卡韦分散片治疗,观察组给予自拟血府逐瘀汤+恩替卡韦分散片治疗,疗程均为48周;观察两组患者治疗前后的临床症状体征改善情况、肝功能指标、肝纤维化相关指标以及肝脏影像学指标变化情况。结果:观察组治疗后临床症状体征改善情况优于对照组(P0.05);观察组治疗后较对照组肝功能指标(ALT、AST、ALB、TBIL)改善程度显著要优(P0.05);观察组治疗后较对照组肝纤维化指标改善程度显著要优(P0.05);观察组治疗后较对照组门静脉的内径、脾脏厚度显著要小(P0.05);观察组治疗后较对照组HBe Ag转阴率显著要高(P0.05);结论:慢性乙型肝炎肝纤维化采取恩替卡韦联合自拟血府逐瘀汤治疗较单一恩替卡韦治疗的临床疗效更显著,优于值得临床推广。     

中国慢性乙肝初治患者逆转录区预存耐药突变流行情况分析

为全面了解中国慢性乙型肝炎病毒初治患者逆转录区预存耐药突变的流行情况,以期对抗病毒药物的选择使用提供帮助,本研究通过对NCBI核酸数据库进行数据挖掘,找出所有中国慢性乙型肝炎病初治患者的逆转录区序列。然后用MEGA 5.0进行序列的比对和耐药分析。研究发现,经典的耐药相关变异罕见(A181T, 0.2%;M250L, 0.2%),但非经典的耐药变异总流行率很高(33.4%, 172/515),且主要存在于基因C型(基因C型:37.8%比基因B型:16.09%, p<0.01);针对拉米夫定的耐药突变最常见(27.18%),而恩替卡韦和替诺福韦以及替比夫定的耐药突变则比较少见(0%~3.3%)。但值得注意的是,在基因B型患者中,恩替卡韦及其与拉米夫定的联合耐药突变率均相对较高(10.34%和9.02%)。虽然,需要进一步大样本临床试验的证实,但是,这仍然提示中国慢性乙型肝炎病毒预存耐药情况需要引起大家的重视。     

恩替卡韦联合胸腺肽α1 治疗慢性乙型肝炎疗效研究

目的:观察和比较恩替卡韦联合胸腺肽α1治疗HBeAg阳性慢性乙型肝炎的疗效。方法:选取我院58例HBeAg阳性慢性乙型肝炎患者分成联合组和对照组。联合组28例,初始同时使用恩替卡韦及胸腺肽α124周,之后停胸腺肽α1继续用恩替卡韦至48周。对照组30例,单用恩替卡韦0.5mg/d,48周。定期检测ALT复常率,HBVDNA转阴率,HBeAg/抗HBe血清转换率,肝纤维化组合,Fibroscan评分两组在治疗结束时进行疗效评价。结果:24周时两组ALT复常率无差异显著性(P>0.05),联合组和对照组HBV DNA阴转率在24周、48周时均差异有显著性(P<0.05)。联合组与单用组HBeAg血清转换率在第24周、48周时,两组比较差异均有显著性(P<0.05)。肝纤维化组合各指标(HA,LN,PⅢP,Ⅳ型胶原),Fibroscan评分两组治疗48周后比较差异均有显著性(P<0.05),且两组治疗前后差异联合组更显著。治疗过程中,未发现明显副作用。结论:恩替卡韦联合胸腺肽α1治疗HBeAg阳性慢性乙型肝炎,安全性与耐受性良好,联合组在ALT复常率,HBeAg血清转换率和HBV DNA转阴率,抗肝纤维化的疗效上显著优于单用恩替卡韦组。     

恩替卡韦改善了乙型肝炎病毒所致急性肝衰竭的预后

目的：阐明乙型肝炎相关急性肝衰竭的预后因素和恩替卡韦的疗效。方法：本研究回顾性选取了47名因感染乙型肝炎病毒而明确诊断急性肝衰竭的患者,其中5名短期内行肝移植手术被排除,其余42名患者的数据被总结分析。结果：42名患者中12名患者服用了恩替卡韦,在诊断之初,服用恩替卡韦组和未服用恩替卡韦组的一般情况基本相当。使用与未使用恩替卡韦者的生存率分别为67%和23%,此外,年龄〉45岁和没有服用恩替卡韦是不良预后的两个独立相关因素。在年龄〉45岁的患者中使用恩替卡韦和未使用恩替卡韦者的存活率分别为50%和8%。结论：本研究证实了恩替卡韦对乙肝相关急性肝衰竭的治疗作用,我们建议所有乙型肝炎病毒引起的急性肝衰竭患者均应尽早开始恩替卡韦抗病毒治疗。     

内江地区慢性乙型肝炎患者的基因型及拉米夫定联合阿德福韦酯抗病毒治疗效果

目的探讨内江地区慢性乙型肝炎患者的基因型及拉米夫定联合阿德福韦酯抗病毒的治疗效果。方法将201例慢性乙型肝炎患者进行HBV基因型的测定,其中120例HBeAg(+)慢性乙型肝炎患者随机分为三组:A组、B组和C组,每组40例。A组给予拉米夫定(LAM)治疗;B组给予恩替卡韦(ETV)治疗;C组给予LAM联合阿德福韦酯(ADV)治疗,比较治疗情况。结果 201例慢性乙型肝炎患者中B型119例(59.2%),C型68例(33.8%),B/C混合型10例(5.0%),未知型4例(2.0%),各分型之间的性别、年龄差异无统计学意义(P0.05)。C型感染者HBeAg阳性率为86.8%,显著高于B型的51.3%(P0.05)。HBeAg(+)的3组患者治疗12、24和48周时,B组和C组患者的ALT复常率、HBV DNA阴转率及48周时的HBeAg血清转换率均显著高于A组(P0.05);C组患者与B组比较差异无统计学意义(P0.05)。治疗期间均未见不良反应发生。C组患者(包括B型19例、C型21例)中B型的HBV DNA阴转率及HBeAg血清转换率显著高于C型(P0.05)。结论地处西南方的内江地区慢性乙型肝炎患者主要以B型为主,C型次之,B型和C型共占93.0%,其他型别仅占较少部分。ETV方案或LAM联合ADV方案治疗HBeAg(+)慢性乙肝疗效优于LAM治疗。初始LAM联合ADV治疗基因B型HBeAg(+)慢性乙型肝炎疗效优于C型。     

恩替卡韦治疗HBeAg阳性乙型肝炎临床观察

目的：探讨恩替卡韦治疗HBeAg阳性乙型肝炎的疗效与安全性。方法：140例慢性乙肝患者随机分为2组：观察组予恩替卡韦0．5mg／d,对照组予拉米夫定100mg／d,疗程均为48周。观察两组HBVDNA阴转率、ALT复常率、HbeAg血清转换率以及不良反应发生情况。结果：在治疗12周后,观察组与对照组HBVDNA阴转率分别为47．1％、22．9％（P〈0．01）,ALT复常率分别为51．4％、31．4％（P〈0．05）,在治疗48周后,观察组与对照组HBVDNA阴转率分别为88．6％、48．6％（P〈0．01）,ALT复常率分别为90．0％、72．9％（P〈0．01）。HbeAg血清转换率无统计学差异,两组患者未见严重不良反应。结论：恩替卡韦治疗HBeAg阳性乙肝患者,较拉米夫定起效快、作用强,且安全性好。     

中西医联合治疗e抗原阳性慢性乙肝临床疗效观察

目的探讨核苷类似物恩替卡韦分散片（ETV）联合冬虫夏草治疗e抗原阳性慢性乙肝临床疗效。方法2010年1月到2012年12月洞头县人民医院门诊e抗原阳性慢性乙肝患者104例,随机分为治疗组和对照组,每组52例,对照组应用恩替卡韦分散片单药治疗,治疗组应用恩替卡韦分散片联合冬虫夏草制剂金水宝胶囊治疗,48周为观察终点。结果两组A肌复常率及HBV—DNA阴转率在治疗过程中差异均无统计学意义,治疗12周及24周后,两组e抗原转阴率、血清转换率差异亦无统计学意义,但治疗48周后,治疗组e抗原转阴率、血清转换率显著高于对照组（分别为0．47US0．41,0．25w0．22,P均〈0．05）。结论应用恩替卡韦分散片（ETV）抗病毒治疗联合冬虫夏草制剂金水宝可以提高e抗原转阴率、血清转换率。     

Antiviral therapy against chronic hepatitis B in Brazil: high rates of lamivudine resistance mutations and correlation with HBV genotypes

The effectiveness of antiviral treatments of chronic hepatitis B has been poorly studied in Brazil. Here, hepatitis B virus (HBV) DNA positivity, drug resistance mutations and their association with HBV genotypes were evaluated in chronically HBV-infected patients under different drug regimens in Brazil. The study involved 129 patients under interferon or nucleos(t)ide analogue therapy for a median treatment time of 12 months. One hundred and five (81%) of these patients were treated with lamivudine (LAM), either in monotherapy or in combination with newer drugs, such as entecavir (ETV) or tenofovir (TDF). High (37.5-100%) rates of HBV DNA positivity were observed with all but one drug regimen (LAM + ETV). However, patients that were treated with ETV alone, TDF alone or with LAM combination therapies had a mean viral load that was 3-4 log lower than patients treated with LAM monotherapy. Of the patients treated with LAM, 47% developed resistance mutations. HBV genotypes A (59.1%), D (30.3%) and F (9.1%) were found. There was no association between the presence of LAM resistance mutations and genotypes, HBeAg status or treatment duration. Nevertheless, the rtM204V mutation was observed more frequently (12/13, 92%) in genotype A than in the others (p = 0.023). Six out of nine isolates that contained the rtM204I mutation belonged to genotype D and half of them displayed a single mutation. Genotype D isolates with the rtM204V variant preferentially displayed a triple mutation, while genotype A preferentially displayed a double mutation (p = 0.04).     

Substitution at rt269 in Hepatitis B Virus Polymerase Is a Compensatory Mutation Associated with Multi-Drug Resistance

The emergence of compensatory mutations in the polymerase gene of drug resistant hepatitis B virus (HBV) is associated with treatment failure. We previously identified a multi-drug resistant HBV mutant, which displayed resistance towards lamivudine (LMV), clevudine (CLV), and entecavir (ETV), along with a strong replication capacity. The aim of this study was to identify the previously unknown compensatory mutations, and to determine the clinical relevance of this mutation during antiviral therapy. In vitro mutagenesis, drug susceptibility assay, and molecular modeling studies were performed. The rtL269I substitution conferred 2- to 7-fold higher replication capacity in the wild-type (WT) or YMDD mutation backbone, regardless of drug treatment. The rtL269I substitution alone did not confer resistance to LMV, ETV, adefovir (ADV), or tenofovir (TDF). However, upon combination with YMDD mutation, the replication capacity under LMV or ETV treatment was enhanced by several folds. Molecular modeling studies suggested that the rtL269I substitution affects template binding, which may eventually lead to the enhanced activity of rtI269-HBV polymerase in both WT virus and YMDD mutant. The clinical relevance of the rtL269I substitution was validated by its emergence in association with YMDD mutation in chronic hepatitis B (CHB) patients with sub-optimal response or treatment failure to LMV or CLV. Our study suggests that substitution at rt269 in HBV polymerase is associated with multi-drug resistance, which may serve as a novel compensatory mutation for replication-defective multi-drug resistant HBV.     

阿德福韦酯与拉米夫定治疗慢性乙肝的疗效对比

目的:比较阿德福韦酯与拉米夫定治疗慢性乙肝的远期疗效。方法:回顾性分析2012年5月至2014年5月我院收治的80例慢性乙肝患者的临床资料,随机分为研究组和对照组,每组各40例。研究组患者给予阿德福韦酯治疗,对照组患者给予拉米夫定治疗。观察两组患者不同时段肝功能指标复常率、病毒量转阴率、乙肝E抗原(HBe Ag)转阴率、粒细胞降低率及乙肝病毒脱氧核糖核酸(HBV-DNA)抑制率,并比较两组患者不良反应发生率。结果:研究组患者肝功能指标复常率、血病毒量转阴率、Hbe Ag转阴率均显著高于对照组同期对应值,差异具有统计学意义(P0.05),但两组患者血粒细胞降低率无显著差异(P0.05);研究组患者HBV-DNA水平总抑制率高于对照组,差异有统计学意义(P0.05);两组患者均无严重不良反应发生(P0.05)。结论:阿德福韦酯治疗慢性乙肝的疗效更显著,能有效抑制HBV-DNA复制且安全性较高。     

Comparison of the Efficacy of Entecavir and Tenofovir in Nucleos(T)ide Analogue-Experienced Chronic Hepatitis B Patients

The efficacy of entecavir (ETV) and tenofovir (TDF) for the treatment of nucleos(t)ide analogue (NA)-experienced chronic hepatitis B (CHB) patients has been little studied. Here, we compare the efficacy of both ETV and TDF in NA-experienced CHB patients without detectable genotypic resistance. This retrospective cohort study included consecutive NA-experienced patients who had neither current nor previous genotypic resistance and had received ETV or TDF for at least 6 months. Overall, 202 patients (146 patients in the ETV group and 56 in the TDF group) were analyzed. The cumulative probabilities of complete virologic suppression (CVS) at month 12 were 76.1% in the ETV group and 95.0% in the TDF group (P<0.001), respectively. The TDF-treated group achieved CVS more rapidly than the ETV group for both Hepatitis B e antigen (HBeAg)-negative and -positive patients (P = 0.006 and < 0.001, respectively), and for those with both low (< 2,000 IU/mL) and high (≥ 2,000 IU/mL) HBV DNA levels (P = 0.01 and 0.002, respectively). TDF group had an increased probability of achieving CVS (hazard ratio, 2.242; 95% confidence interval, 1.587–3.165; P = 0.001), after adjustment for HBV DNA level, the presence of HBeAg, and a history of CVS during prior treatment. During the treatment period, 23 patients (15.8%) in the ETV group developed virologic breakthrough, compared to none in the TDF group. The cumulative probabilities of developing virologic breakthrough and ETV-resistance at month 24 were 9.7% and 5.3%, respectively. In conclusion, TDF is preferable to ETV for achieving CVS in NA-experienced CHB patients without genotypic resistance.